The long term objective is to develop new ways in which NMR spectroscopy can be used to solve two problems in the field of protein chemistry: (1) the way in which the sequence of protein determines its three dimensional structure, dynamic properties, and thus, its function: and (2) the molecular basis for enzyme catalysis, along with the mechanisms by which proteins interact with other molecules leading to changes in their function. The problem of sequence-structure-reactivity will be investigated through one-and two-dimensional [(1H, 1H) and (13C, 1H)] Fourier transform NMR studies of a series of ovomucoids. The ovomucoids provide an unparalleled opportunity for this kind of research because of the availability of over 90 sequences of ovomucoid structural domains, detailed knowledge about the reactivities of these proteins as serine proteinase inhibitors with different serine proteinases, and x-ray crystallographic structures of one inhibitor and one inhibitor-proteinase complex. It is hoped that, through NMR measurements, molecular dynamics simulations, electrostatic calculations, and model building by computer graphics, rules can be developed for the prediction of structural and functional properties (such as protein conformation, molecular dynamics, pKa values, and protein-proteinase association constants). The problem of enzyme catalysis and its control is being studied with a series of serine proteinases and with phosphoglucomutase. Multinuclear NMR spectroscopy and stopped-flow optical spectroscopy will be used to investigate "trapped" intermediates and inhibited species. The objectives are (1) to determine the sequence, structural characteristics, and energetics of intermediates in the reaction pathways; and (2) to elucidate the mechanisms by which activity is lowered in inhibited forms of the enzymes or in the zymogen precursors of serine proteinases. Serine proteinases and their inhibitors play key roles in biochemistry, and variations of their levels have been implicated in several human diseases. Ovomucoid belongs to the same family of inhibitors as the human secretory trypsin inhibitor. Phosphoglucomutase is a central enzyme in the glycolytic pathway.